Life Extension Magazine February 2009
As We See It
The Cholesterol Controversy
By William Faloon
By William Faloon
Life Extension Magazine February 2009
As We See It
By William Faloon
As we enter the year 2009, a heated debate continues about the role of cholesterol in the development of atherosclerosis and heart disease. Based on our analysis, both sides still have it wrong!
Almost comical is the role reversal this controversy has taken. When progressive individuals first proposed that high cholesterol increases heart attack risk, the medical establishment ridiculed the idea. The FDA went so far as to make it illegal for food companies to claim that diets low in saturated fat and cholesterol had any relationship to artery disease. (Note: High-saturated fat diets cause blood cholesterol to spike.)
The dispute raged for decades until the medical establishment (and the FDA) not only embraced the concept that high cholesterol causes heart attacks, but claimed this scientific area their exclusive domain.1-5 Many of today’s complementary medicine practitioners, who would have been early proponents of low-saturated fat diets, now question the association between cholesterol and vascular disease.
The fact that confusion still exists over this straightforward medical principle helps explain why atherosclerotic disease remains today’s leading preventable killer.
Early History of Cholesterol and Arterial Disease
If we travel back to 1913, we would learn of an impressive study showing that rabbits fed a high-cholesterol diet develop atherosclerotic lesions that closely resemble those seen in humans.6 This research was initially criticized because rabbits are plant eaters whose normal diets are not the same as humans. When dogs and rats are fed high-cholesterol diets, they do not develop artery disease. It was later discovered that dogs and rats efficiently convert cholesterol to bile acids that are excreted. When these excretion mechanisms are blocked, however, dogs and rats do develop atherosclerosis in response to cholesterol feeding.
The cholesterol theory gained a bit more credibility when atherosclerotic lesions were readily induced in guinea pigs,7,8 goats,9 hens, parrots,10 and even primates11 in response to cholesterol elevation.
Interestingly, the first hints that high cholesterol caused atherosclerosis in humans occurred back in 1889.2,12 A doctor reported a case of a child with a rare genetic disorder that caused massive overproduction of cholesterol. The child died suddenly at age 11. An autopsy revealed extensive atherosclerotic-like lesions in large arteries.
It was not until 1939 that a publication in the Archives of Internal Medicine pulled together the evidence linking this rare genetic disorder (familial hyper-cholesterolemia) to coronary artery disease.2,13 It was argued back then, however, that the extraordinarily high cholesterol levels in those with this genetic defect could not be extrapolated to people with only moderate cholesterol elevations.
By 1955, the cholesterol-heart attack connection was attracting some respectability. A study was done that measured cholesterol blood levels in people from seven different countries. Citizens of Finland, who ate the most saturated fats, had an average cholesterol reading of over 260 (mg/dL). The Japanese, who consumed the least saturated fat, had average cholesterol readings of a little over 160. Over a 10-year period, the number of fatal heart attacks per 1,000 men was about 70 in Finland and a little less than 5 in Japan. Saturated fat made up 20% of the Finnish diet, but only 2.5% of the Japanese diet.2,14
These findings had a significant impact on the cholesterol debate, but the vast majority of physicians and the federal government still proclaimed that high cholesterol had nothing to do with heart attack risk.
Where Some Researchers Went Wrong
In trying to prove that diets high in saturated fats increase cholesterol levels and subsequent heart attack risk, scientists conducted studies that substituted omega-6-rich polyunsaturated fats (corn oil, safflower oil) in place of saturated fats (butter, lard, meat fats).15-17 While these studies showed reduced cholesterol levels and heart attack rates, the findings were not nearly as impressive as they could have been. This is because these kinds of polyunsaturated fats (corn oil, sunflower oil, safflower oil, etc.) rich in omega-6 fatty acids create inflammatory byproducts and induce LDL oxidation that damages arteries.
During this era of medical ignorance (the 1950s-1960s), the benefits of monounsaturated fats (such as those found in olive oil) and omega-3 fats (such as those found in cold-water fish, flaxseed, and walnut oils) in preventing heart attacks were not recognized. The best that doctors could provide in lieu of dangerous saturated fats was to substitute omega-6 polyunsaturated fats, which then created a dangerous proinflammatory state (due to an imbalance in omega-6 to omega-3 fats).18
The 1960s… More Lost Opportunities
I’ll never forget going to my first funeral and seeing a 42-year-old neighbor lying in a coffin. He had died of a sudden heart attack, but no one talked about how unusual his early death was. That’s because men over age 40 were routinely dying of heart attacks in those days.
Heart attacks and strokes claimed astronomical numbers of lives in the Western world throughout most of the past century. During the early 1960s, for example, the number of acute fatal heart attacks in younger men was substantially higher than today.19-21 A lot of this had to do with cigarette smoking and the high-saturated fat diet that was a staple in most households.
By the early 1960s, however, the theory that one could reduce their heart attack risk by avoiding saturated fats had taken hold at least in the alternative medicine community. Even the American Heart Association went on record as early as 1961 with the following closely guarded statement:
“Those people who have had one or more atherosclerotic heart attacks or strokes may reduce the possibility of recurrences by such a change in diet.”2,22
Based on a wave of studies showing reductions in heart attack incidence in those who reduced their saturated fat intake, nutritionists and alternative doctors were finally espousing heart-healthy diets. The FDA responded by criminalizing the commercial dissemination of this information by the food industry. Heart attacks claimed about seven million American lives in the 1960s.20 The FDA’s suppression of the link between poor diet and heart attack risk kept funeral businesses thriving.
The Great Cholesterol Debates
In 1969, an American Heart Association spokesperson stated that those with excess cholesterol levels should be treated medically. This doctor went on to state, “in short, we have come ... to the point where we are probably preventing a disease that was considered to be an inevitable accompaniment of aging not very long ago.”26
The American Heart Association met with fierce criticism from prominent cardiologists who continued to proclaim there was no evidence that cholesterol reduction conferred protection against heart attacks. These attacks on the cholesterol theory of heart disease were published in the leading medical journals of the day.
Regrettably, it was not until 1984 that the medical establishment formally recognized the relationship between high cholesterol and heart attack incidence.27
Nathan Pritikin… An Early Hero of Mine
I will never forget as a teenager seeing a televised debate between Nathan Pritikin and a mainstream cardiologist. Pritikin explained how very low-fat diets could reverse coronary atherosclerosis, whereas the cardiologist ridiculed the notion.
I knew little about heart attacks back then, other than the fact that my family members and neighbors were having them on a regular basis. I also witnessed the poor diets these heart attack victims ate, which made Nathan Pritikin’s arguments all the more convincing to me.
What was so remarkable about Nathan Pritikin was that he had no medical training. In 1957, at age 40, Pritikin was diagnosed as having heart disease. Faced with a lifetime of ever-increasing disability, he pored over the scientific literature and formulated a diet and exercise program to treat his disease.28 After nine years of trial and error, he had cured himself.
Long before the medical establishment acknowledged that something as simple as diet might be causing serious illnesses, Pritikin had created a scientifically sound program using food and exercise as medicine. This revolutionary departure from the flawed theories of the 1950s caused him to become a public enemy of the medical establishment. Nathan Pritikin’s healthy diet program did more than reverse heart disease. Patients who came to his clinic often saw their type 2 diabetes, arthritis, and hypertension disappear.29,30
Despite these clinical successes, Nathan Pritikin was ceaselessly attacked by doctors as being a charlatan. For much of the 1970s, Nathan Pritikin waged a public battle with government and private health agencies, as well as with the American Medical Association. The medical establishment doggedly refused to accept that what one ate had anything to do with their risk of heart disease.
Pritikin was so confident that he was reversing heart disease with healthy diets that he ordered his own body autopsied after his death. Almost 30 years after being diagnosed with irreversible coronary artery disease, the autopsy showed his arteries were akin to those of a young man and clear of any signs of heart disease.31
In 1987, two years after Nathan Pritikin’s death, the Journal of the American Medical Association announced a study that showed regression of atherosclerosis in the coronary arteries of humans who reduced their blood cholesterol by a similar degree as were accomplished at the Pritikin Longevity Centers.32 Numerous subsequent studies confirmed that Nathan Pritikin was scientifically correct…and the medical establishment’s position fatally flawed.33-36
Tens of millions of Americans needlessly perished because the role of cholesterol in causing heart disease was not recognized nearly as early as it should have been.
What is Cholesterol?
Cholesterol is a lipid (fat) that is chemically classified as a sterol. It provides critically important functions in the body such as building and maintaining cell membranes. Cholesterol also functions as a precursor to hormones like testosterone and fat-soluble vitamins.
While cholesterol is essential to life, the lipoprotein it is bound to plays a role in whether it injures or protects the arterial wall. Since cholesterol is insoluble in blood, it is transported in the circulatory system by lipoproteins.
LDL (low-density lipoprotein) transports cholesterol to the cells, whereas HDL (high-density lipoprotein) transports cholesterol away from the cells.
When one has excess LDL, too much cholesterol can be deposited into the arterial wall. Insufficient HDL, on the other hand, impairs cholesterol transport away from the arterial wall (for disposal in the liver). Too much LDL and/or not enough HDL can thus set the stage for atherosclerosis. These simple facts, however, explain only part of the problem.
Danger of Oxidized LDL
The over-promotion of “statin”drugs has resulted in today’s cardiologists focusing on getting their patients’ LDL and total cholesterol down as low as possible. Pharmaceutical company advertising has made it appear as if the only cause of atherosclerosis is excess LDL and cholesterol.
Beginning in 1979, however, researchers made discoveries indicating that it is the oxidation of LDL that results in the most arterial damage.37-39 Thousands of studies now reveal how oxidized LDL contributes to the atherosclerotic process from start to finish.
There are doctors who argue that atherosclerosis is all about inflammation and response to endothelial injury and has nothing to do with LDL cholesterol. What these doctors overlook is the fact that oxidized LDL injures endothelial cells and causes inflammation!40-46
Oxidized LDL causes endothelial cells to secrete “adhesion molecules” that allow white blood cells to penetrate the inner lining of the artery (the endothelium). This is where initial fatty streaks and atherosclerotic plaques develop.47
Oxidized LDL turns on white blood cell gene expression that enables them to convert into foam cells, which results in continuous accumulation of oxidized LDL in the atherosclerotic plaque.48
Oxidized LDL initiates an inflammatory process by causing foam cells to secrete molecules that attract proinflammatory cells.47
Oxidized LDL enhances the process whereby immune cells, foam cells, smooth muscle cells, and endothelial cells degrade collagen, which leads to the rupture of the fibrous plaque.49
The endothelium requires nitric oxide to function properly. A hallmark characteristic of endothelial dysfunction is a lack of nitric oxide. Oxidized LDL impairs the endothelial cells’ ability to produce nitric oxide.50
As you may surmise by now, both absolute LDL level and LDL oxidation are involved in atherosclerotic processes and heart attack risk.
Common Sense Approaches to Heart Attack Prevention
Financial bias, apathy, and scientific ignorance have resulted in most Americans failing to protect themselves against today’s leading crippler and killer… atherosclerosis.
Some cardiologists erroneously believe that if all their patients took a statin drug and aspirin, coronary artery disease would disappear. Equally disturbing are doctors who claim that that aging people should not worry about their LDL levels.
For 29 years, we at Life Extension have emphasized that atherosclerosis has many underlying causes.51 Our findings have been validated in many subsequently published studies.52-54 At the end of this article, we have reprinted an updated version showing 17 daggers aimed at the heart, each dagger representing an independent risk factor for developing coronary artery disease. Fortunately, most Life Extension members are already taking nutrients, hormones, and sometimes drugs to protect against every one of these cardiac risk factors.
When it comes to inhibiting LDL oxidation, members should find comfort in knowing they have been taking supplements that have been confirmed to dramatically inhibit LDL oxidation. A number of studies document the ability of ubiquinol CoQ10 to protect against LDL oxidation better than lycopene, alpha tocopherol, and other lipid-soluble antioxidants.55-59 Some of these studies show that alpha tocopherol (vitamin E) can turn into an LDL pro-oxidant unless ubiquinol is also present.60 These studies help explain the inability of the alpha form of vitamin E by itself to significantly reduce heart attack rates in certain populations.
Perhaps no other nutrient has demonstrated better anti-LDL oxidation effects than pomegranate. In a clinical study, human subjects taking pomegranate showed a beneficial 35% reduction in carotid intima-media thickness accompanied by a 45% improvement in carotid blood flow. As evidenced by the chart above, pomegranate improved markers related to LDL oxidation by up to 130%!61
These kinds of impressive study results, showing how LDL oxidation can be suppressed, might tempt some people to ignore dangerously high LDL blood levels. We at Life Extension strongly advise against this. The chart below vividly shows the sharp increase in coronary artery disease risk as LDL concentrations increase in the blood.62
Keep Your LDL Levels Below 100
Atherosclerosis remains the leading cause of death in the Western world.63 Eastern populations who are switching to high-fat Western diets are seeing vascular disease rates spiral upwards. We cannot ignore almost 100 years of research showing that excess LDL-bound cholesterol is a coronary risk factor.
While there may someday be a definitive finding that something as simple as pomegranate provides complete protection against LDL oxidation, and therefore excess LDL itself, we don’t have these data confirmed today.
You have entrusted us to provide you with an accurate analysis of the available scientific literature to keep you alive in good health. We therefore reiterate our 29-year recommendation that healthy members keep their LDL levels below 100 mg/dL.
Very high-risk groups (e.g., smokers or those with diabetes, abdominal obesity, a recently sustained heart attack, low HDL, high triglycerides, or known coronary artery disease) should strive for a 70-75 mg/dL LDL target level. (Note: Those who drive LDL down to these very low levels should use blood tests to make sure they are not also suppressing critical hormones like testosterone and DHEA.)
The chart on top of this page clearly demonstrates that in people who have already suffered a coronary event, each progressive LDL elevation increases the risk of a second event. In this study, cardiac disease incidence was 80% greater in those with an LDL reading over 94 mg/dL compared with those whose LDL was under 54 mg/dL.64
Tying it all Together
In reviewing the history of dietary fats and heart disease risk, a number of interesting facts emerge. Nathan Pritikin put a lot of the pieces together when he mandated that virtually all dietary fat should be eliminated (less than 10% total calories from fat). This protected his followers against the atherogenic effects of both saturated fat and dangerous omega-6-rich polyunsaturated fat sources like corn, soybean, safflower, and sunflower oils. The problem is that adhering to Pritikin’s very strict diet is difficult for the vast majority of people.
Fortunately, we know today that following a low-saturated fat, Mediterranean-type diet with lots of natural polyphenol antioxidants provides huge cardioprotective benefits.65 We have also acquired the knowledge that specific fats (omega-3s and certain monounsaturated fats) are extremely beneficial in reducing vascular disease risk.66,67
As we report in this issue of Life Extension, a large number of studies continue to validate the ability of low-cost plant polyphenols to not only protect against LDL oxidation, but to also boost beneficial HDL and lower absolute LDL levels in the blood.68-76
It may thus be possible for many aging humans to achieve optimal blood lipid status using an integrative approach to support healthy cholesterol levels and reduce oxidant stress… without resorting to prescription drugs.
Natural Protection at the Lowest Prices
For 21 consecutive years, Life Extension members have taken advantage of the annual Super Sale to stock up on a large supply of their favorite nutrient formulations.
During this annual winter event, every Life Extension product is discounted so that members can obtain our most up-to-date formulas at the lowest prices of the year.
We recently upgraded our most popular products to provide even more life-protecting nutrients. Until February 2, 2009, members can obtain extra discounts on every one of these formulas during our once-a-year Super Sale.
For longer life,
1. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part I. J Lipid Res. 2004 Sep;45(9):1583-93.
2. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans. J Lipid Res. 2005 Feb;46(2):179-90.
3. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia. J Lipid Res. 2005 Oct;46(10):2037-51.
4. Steinberg D. The pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part IV: the 1984 coronary primary prevention trial ends it—almost. J Lipid Res. 2006 Jan;47(1):1-14.
5. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the statins and the end of the controversy. J Lipid Res. 2006 Jul;47(7):1339-51.
6. Fleissig J. Uber die bisher als Riesenzellensarkome (Myelome) bezeichneten Granulationsgeschwulste der Sehnenschiden. Dtsch Z Chir. 1913;122:239-65.
7. Bailey CH. Observations on cholesterol-fed guinea pigs. Proc Soc Exper Biol. 1915;13:60-2.
8. Anitschkow N. Ueber die experimentelle Atherosklerose der Aorta beim Meerschwinchen. Beitr Pathol Anat. 1922;70:265-81.
9. Chalatow S. Bemerkungen an den Arbeiten uber Cholesterinsteatose. Virchows Arch A Pathol Anat Histol. 1929;272:691-708.
10. Anitschkow N. Einige Ergebnisse der experimentellen Atherosklerosforschung. Verhandlungen den Deutschen Pathologischen Gesellschaft. 1925;20:149-54.
11. Clarkson TB. Animal models of atherosclerosis. Adv Vet Sci Comp Med. 1972;16:151-73.
12. Lehzen G, Knauss K. Ueber Xanthoma multiplex planum, tuberosum, mollusciformis. Virchows Arch A Pathol Anat Histol. 1889;116:85-104.
13. Müller C. Angina pectoris in hereditary xanthomatosis. Arch Intern Med. 1939; 64:675-700.
14. Keys AC. Aravanis HW, Blackburn FS, et al. Epidemiological studies related to coronary heart disease: characteristics of men aged 40–59 in seven countries. Acta Med Scand. 1966;460(Suppl.):1-392.
15. Olson F, Michaels G, Partridge JW, et al. The use of formula diets administered via polyethylene tube or orally for constant intake (balance) studies. J Clin Nutr. 1953 Jan;1(2):134-9.
16. Ahrens EH, Jr, Dole VP, Blankenhorn DH. The use of orally-fed liquid formulas in metabolic studies. Am J Clin Nutr. 1954 Sep;2(5):336-42.
17. Leren P. The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Med Scand Suppl. 1966;466:1-92.
18. Kiecolt-Glaser JK, Belury MA, Porter K, et al. Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults. Psychosom Med. 2007 Apr;69(3):217-24.
19. US Health Resources Administration. A comparison of levels of serum cholesterol of adults 18-74 years of age in the United States in 1960-62 and 1971-74. Vital & Health Statistics of The National Center for Health Statistics, US Department of Health and Education Welfare. 1977 Feb;22(5).
20. Available at: http://www.cdc.gov/nchs/data/statab/dx196067.pdf. Accessed September 29, 2008.
21. Higgins M, Thom T. Trends in CHD in the United States. Int J Epidemiol. 1989;18(3 Suppl 1):S58-66.
22. Anon. Diet and the possible prevention of coronary atheroma; a council statement. JAMA. 1965 Dec 6;194(10):1149-50.
23. Gofman JW, Lindgren F. The role of lipids and lipoproteins in atherosclerosis. Science. 1950 Feb 17;111(2877):166-71.
24. Gofman JW. Serum lipoproteins and the evaluation of atherosclerosis. Ann NY Acad Sci. 1956 Nov 16;64(4):590-5.
25. Dobbin EV, Gofman HF, Jones HC, Lyon L, Young C. The Low-Fat, Low-Cholesterol Diet. Garden City, NY: Doubleday; 1951.
26. Steinberg D. Progress, prospects and provender. Chairman’s address before the Council on Arteriosclerosis, American Heart Association, Dallas, Texas, November 12, 1969. Circulation. 1970 Apr;41(4):723-8.
27. Available at: http://consensus.nih.gov/1984/1984Cholesterol047html.htm. Accessed October 1, 2008.
28. Pritikin N. The Pritikin diet. JAMA. 1984 Mar 2;251(9):1160-1.
29. Barnard RJ, Lawani LO, Martin DA, et al. Effects of maturation and aging on the skeletal muscle glucose transport system. Am J Physiol. 1992 May;262(5 Pt 1):E619-26.
30. Roberts CK, Barnard RJ. Effects of exercise and diet on chronic disease. J Appl Physiol. 2005 Jan;98(1):3-30.
31. Hubbard JD, Inkeles S, Barnard RJ. Nathan Pritikin’s heart. N Engl J Med. 1985 Jul 4;313(1):52.
32. Blankenhorn DH, Nessim SA, Johnson RL, et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987 Jun 19;257(23):3233-40.
33. Roberts CK, Chen AK, Barnard RJ. Effect of a short-term diet and exercise intervention in youth on atherosclerotic risk factors. Atherosclerosis. 2007 Mar;191(1):98-106.
34. Roberts CK, Won D, Pruthi S, et al. Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors. J Appl Physiol. 2006 May;100(5):1657-65.
35. Roberts CK, Vaziri ND, Barnard RJ. Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability. Circulation. 2002 Nov 12;106(20):2530-2.
36. Anderson JW, Konz EC, Jenkins DJ. Health advantages and disadvantages of weight-reducing diets: a computer analysis and critical review. J Am Coll Nutr. 2000 Oct;19(5):578-90.
37. Henriksen T, Mahoney EM, Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci USA. 1981 Oct;78(10):6499-503.
38. Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis. 1983 May;3(3):215-22.
39. Quinn MT, Parthasarathy S, Fong LG, Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA. 1987 May;84(9):2995-8.
40. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26.
41. Ross R. The pathogenesis of atherosclerosis—an update. N Engl J Med. 1986 Feb 20;314(8):488-500.
42. Yla-Herttuala S, Palinski W, Rosenfeld ME, et al. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest. 1989 Oct;84(4):1086-95.
43. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915-24.
44. Berliner JA, Navab M, Fogelman AM, et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995 May 1;91(9):2488-96.
45. Suits AG, Chait A, Aviram M, Heinecke JW. Phagocytosis of aggregated lipoprotein by macrophages: low density lipoprotein receptor-dependent foam-cell formation. Proc Natl Acad Sci USA. 1989 Apr;86(8):2713-7.
46. Palinski W, Rosenfeld ME, Yla-Herttuala S, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci USA. 1989 Feb;86(4):1372-6.
47. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006 Feb;83(2):456S-60S.
48. Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998 Apr 17;93(2):241-52.
49. Libby P. The molecular mechanisms of the thrombotic complications of atherosclerosis. J Intern Med. 2008 May;263(5):517-27.
50. Zhang WZ, Venardos K, Finch S, Kaye DM. Detrimental effect of oxidized LDL on endothelial arginine metabolism and transportation. Int J Biochem Cell Biol. 2008;40(5):920-8.
51. Faloon W. A lethal misconception of epidemic proportion. Life Extension. 2007 May;13(5):7-14.
52. Danesh J, Lewington S, Thompson SG, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005 Oct 12;294(14):1799-809.
53. Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Testosterone as a protective factor against atherosclerosis—immunomodulation and influence upon plaque development and stability. J Endocrinol. 2003 Sep;178(3):373-80.
54. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001 May 16;285(19):2481-5.
55. Stocker R, Bowry VW, Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci USA. 1991 Mar 1;88(5):1646-50.
56. Frei B, Kim MC, Ames BN. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci USA. 1990 Jun;87(12):4879-83.
57. Thomas SR, Neuzil J, Stocker R. Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for coenzyme Q in atherogenesis? Mol Aspects Med. 1997;18(Suppl):S85-103.
58. Mohr D, Bowry VW, Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta. 1992 Jun 26;1126(3):247-54.
59. Kontush A, Hubner C, Finckh B, Kohlschutter A, Beisiegel U. Antioxidative activity of ubiquinol-10 at physiologic concentrations in human low density lipoprotein. Biochim Biophys Acta. 1995 Sep 14;1258(2):177-87.
60. Bowry VW, Mohr D, Cleary J, Stocker R. Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein. J Biol Chem. 1995 Mar 17;270(11):5756-63.
61. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423-33.
62. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13;110(2):227-39.
63. Available at: http://www.cdc.gov/nchs/data/nvsr/nvsr56/nvsr56_16.pdf. Accessed October 15, 2008.
64. Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6;352(1):20-8.
65. de Lorgeril M, Salen P, Martin JL, et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999 Feb 16;99(6):779-85.
66. Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ. Omega-3 fatty
acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis. 2008 Mar;197(1):12-24.
67. Pérez-Jiménez F, Ruano J, Perez-Martinez P, Lopez-Segura F, Lopez-Miranda J.
The influence of olive oil on human health: not a question of fat alone. Mol Nutr Food Res. 2007 Oct;51(10):1199-208.
68. Aviram M, Fuhrman B. Wine flavonoids protect against LDL oxidation and atherosclerosis. Ann NY Acad Sci. 2002 May;957:146-61.
69. Martin-Nizard F, Sahpaz S, Furman C, et al. Natural phenylpropanoids protect endothelial cells against oxidized LDL-induced cytotoxicity. Planta Med. 2003 Mar;69(3):207-11.
70. Janisch KM, Williamson G, Needs P, Plumb GW. Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin. Free Radic Res. 2004 Aug;38(8):877-84.
71. Sies H, Stahl W, Sevanian A. Nutritional, dietary and postprandial oxidative stress. J Nutr. 2005 May;135(5):969-72.
72. Mursu J, Voutilainen S, Nurmi T, et al. Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans. Free Radic Biol Med. 2004 Nov 1;37(9):1351-9.
73. Baba S, Osakabe N, Kato Y, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Am J Clin Nutr. 2007 Mar;85(3):709-17.
74. Covas MI, Nyyssonen K, Poulsen HE, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006 Sep 5;145(5):333-41.
75. Baba S, Natsume M, Yasuda A, et al. Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different levels of cocoa powder. J Nutr. 2007 Jun;137(6):1436-41.
76. Zern TL, Wood RJ, Greene C, et al. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr. 2005 Aug;135(8):1911-7.
77. Available at: http://www.doctorzebra.com/prez/z_x34mirx_g.htm#zree6#zree6. Accessed October 15, 2008.
78. Available at: http://www.nps.gov/archive/lyjo/ourheartshome/lbj3.htm. Accessed October 15, 2008.